Compelling evidence has shown that inescapable stress, a putative animal model of depression, increases susceptibility to viral diseases such as herpes simplex, influenza, and coxsackie virus infections via alterations in immune function. However, translation of these basic observations into the clinical setting is limited, and the immunological consequences of major depression and their possible clinical relevance to infectious diseases remain unknown. Moreover, immunological studies of depressed subjects have not evaluated disease specific immune measures nor assayed in vivo immune responses that correlate with outcome. This study hypothesizes that older adults with major depression are at increased risk for reactivation of varicella-zoster virus (VZV) infection. Because much evidence indicates that cell mediated immunity plays a critical role in limiting the occurrence of herpes zoster (HZ) and its complications, the effect of major depression on VZV-specific cellular immunity will be examined. Using a disease specific approach, this study will also evaluate the integrity of an integrated, in vivo immune response to VZV vaccine in depressed subjects as compared to controls. The specific aims of this project are to: 1) determine whether major depressive disorder is associated with declines in VZV specific immunity in adults 60 years of age and older; and 2) evaluate whether major depressive disorder attenuates the magnitude or duration of vaccine-stimulated virtue of their older age are at increased risk for HZ and assaying VZV specific immunological measures that are known to correlate with the occurrence and severity of HZ and its complications, this study advances our model, another major strength, will yield substantial new information about how the immune system of depressed subjects responds to an antigen of an infectious pathogen.